This proposal requests funds for the continuation of the Rocky Mountain Smell and Taste Center. Research under the auspices of this center has and will continue to concentrate on cellular level analysis of chemosensory receptor structure and function in humans as well as in model animal systems. The Center consists of the personnel and laboratories of six principal investigators located at the University of Colorado and at Colorado State University. During the proposed grant period emphasis will be placed on correlated structure-function analysis of the olfactory and gustatory receptors and primary sensory neurons at the cellular and tissue levels. The structure and physiology of taste receptors will be analyzed in a variety of preparations. Biopsy material from human ageusics will be analyzed to determine whether a correlation can be made between specific morphological changes and specific ageusic conditions. Basic science studies on gustation include cellular and tissue level analyses of ion flux during taste transduction, possible ultrastructural changes during taste stimulation, and the relationships between taste bud cells and the primary gustatory nerve fibers upon which the receptor cells synapse. In addition, the possible functional role of neuropeptides in taste transduction will be examined. Finally the ultra structure and degree of plasticity of central terminations of the gustatory nerves will be examined. Studies on the olfactory system include ultrastructural studies relating olfactory receptor pathology to specific anosmic states associated with various conditions such as Alzheimer's disease, postviral anosmia, and cocaine use. The possible role of respiratory tree microvillar cells in chemosensation also will be examined. In addition, the synaptic and maturation-dependent ultrastructure of olfactory neurons will be examined. These studies all rely heavily on advanced ultrastructural, electrophysiological, and immunochemical techniques already mastered by the participating principal investigators. The good working relationships between the investigators, research projects and facilities is a major, vital element of the Program Project.